ReviewThe interplay between neuropathology and activity based rehabilitation after traumatic brain injury
Introduction
Physical activity is well known for its beneficial effects on health and its influence on brain structure and function. We will discuss multiple mechanisms behind exercise׳s beneficial effect on enhancement of cognitive functions and neuroprotection. The effects of exercise will also be reviewed within the context of traumatic brain injury (TBI) pathophysiology. Metabolic, neuroendocrine and inflammatory alterations observed after TBI have an influence on the brain׳s response to exercise. Given the dynamic nature of TBI, physical activity is more likely to be beneficial when the timing and intensity of exercise is implemented in a manner that takes into consideration ongoing pathophysiological processes. The importance of timing of exercise interventions will be discussed. In particular we will describe how exercise and metabolic, neuroendocrine and inflammatory responses to TBI ineract. We will translate experimental findings from animal models to clinical practice by addressing “return to play” concerns. Finally, we will discuss the potential of physical activity as a rehabilitative tool following TBI.
Section snippets
Benefits of exercise on the brain
Regularly engaging in physical activity has been associated with a lower incidence of chronic health conditions such as diabetes, cancer, hypertension, stroke, and cardiovascular disease (Haskell et al., 2007, Myers et al., 2002, Booth et al., 2000). Besides being beneficial to overall health, physical exercise has also been associated with enhanced cognitive functioning in children and adults. A meta-analysis found that childhood physical activity was associated with academic achievement, as
Exercise following TBI
As indicated above the beneficial effects of exercise are clearly observed in the intact brain. However, responses to exercise are influenced by multiple pathophysiological processes that are observed after TBI. TBI involves disruptions in ionic, metabolic and physiological homeostasis, all of which culminate into the various cognitive, physical and psychosocial deficits observed in animal models and humans following TBI. Disruptions in these physiological processes can progress over hours,
The interaction between metabolic responses to TBI and exercise
During TBI, damage is sustained to neuronal membranes and axons, resulting in abrupt membrane depolarization (Kawamata et al., 1992, Katayama et al., 1990) and indiscriminate release of excitatory neurotransmitters, particularly glutamate (Hayes et al., 1992). Excessive glutamate release results in activation of N-methyl-D-aspartate (NMDA) receptors and in accumulation of intracellular calcium (Osteen et al., 2004, Osteen et al., 2001, Fineman et al., 1993). Increased calcium influx can lead to
The interaction between neuroendocrine responses to TBI and exercise
Clinical evidence has demonstrated that TBI can cause hypothalamic-pituitary dysfunction, which may delay or interfere with functional recovery from TBI (Krahulik et al., 2010). During the acute phase of recovery from TBI, changes in the neuroendocrine system may be present as part of the adaptive response to TBI (Bondanelli et al., 2005). Initially after TBI, the HPA (hypothalamic-pituitary-adrenal) axis is activated in a trauma-induced stress response, which results in elevated serum cortisol
The interaction between inflammatory responses to TBI and exercise
The pathophysiological changes resulting from TBI can contribute to neuroinflammation and delayed cell death (Stoica and Faden, 2010). Besides exerting effects on neuroplasticity, physical exercise has been associated with neuroprotection mechanisms such as the reduction of cytokines. Cytokines are immune system messengers with pro- or anti-inflammatory properties.
Acutely, a bout of exercise results in a transient increase in the serum concentration of various immunomodulatory proteins,
Impact of exercise on return to play
As indicated above, there appears to be a temporal window of vulnerability after a TBI. Animal studies have demonstrated more disruptions in cellular metabolism and more significant cognitive impairments if a second injury to the brain is sustained during the initial post-TBI recovery period (Shrey et al., 2001, Vagnozzi et al., 2010, Vagnozzi et al., 2008, Vagnozzi et al., 2007, Tavazzi et al., 2007, Kissick and Johnston, 2005, Longhi et al., 2005). This has been a major concern within the
The interaction between exercise and rehabilitation
Exercise has been investigated as a therapeutic agent following TBI in both animal and human studies. In fact, exercise may be a critical component of many therapeutic interventions. For instance, in animal models of TBI, enriched environments (EE) have been utilized to mimic some of the aspects of a clinical rehabilitation environment. Housing an animal with toys, running wheels and other rodents allows for socialization, exploration and interaction beyond that provided by standard laboratory
Conclusions
It has been established through multiple animal studies that exercise exerts positive effects on neuroinflammation, neuroplasticity, neurodegeneration, as well as, cognitive, motor and psychiatric behaviors (Svensson et al., 2015). When addressing physical exercise in the context of TBI, additional factors such as the timing, intensity, quality and duration of exercise along with ongoing neuropathological processes will dictate whether exercise has a beneficial effect on recovery. In
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2022, Brain Research BulletinCitation Excerpt :The idea of non-pharmacological intervention is appealing given the frequency of TBI patients being on multiple medications that present sleep-related side effects. A particular intervention of interest is exercise due to its regulatory effects on both sleep and endocrine function (Chennaoui et al., 2015; Hackney and Lane, 2015; Kreber and Griesbach, 2016). Exercise has been presented as an alternative form of treatment for insomnia (Amiri et al., 2021; Chennaoui et al., 2015; Passos et al., 2014), and has been associated with improvements in health associated with endocrine system functioning (Ball, 2015; Cotman et al., 2007; Stokes et al., 2013).
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2021, Behavioural Brain ResearchCitation Excerpt :In line with this, better outcomes were found in an experimental model of concussion when exercise was started within the first 3 days after injury [47]. However, with higher severity injuries, very early initiation of exercise can result in adverse effects, because the increased energy consumption induced by exercise can prevent coping with the increased energy demands associated to injury and exacerbate the major alterations in brain metabolism produced early after TBI [10]. In addition, from the translational point of view, testing the effectiveness of delayed exercise seems highly relevant, as patients with moderate-severe TBI cannot exercise at the acute stage, when disrupted consciousness and other neurological and non-neurological symptoms requiring intensive care are common.
Why exercise may be beneficial in concussion rehabilitation: A cellular perspective
2019, Journal of Science and Medicine in SportCitation Excerpt :These previously discussed topics can potentially affect several proteins and second messenger pathways, which can also influence genetic expression. Of significant importance are brain-derived neurotrophic factor (BDNF), cyclic adenosine monophosphate (cAMP) response binding protein (CREB), peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1a), mammalian target of rapamyicin (mTOR), and more.21,31–35 These factors are all essential in facilitating neuroprotection and synaptic plasticity in the brain, as well as overall cell efficiency and neuronal homeostasis.11,12,35–37